Protein blocking may activate immune response to HIV

LOS ANGELES, Dec. 23 (UPI) -- Researchers at UCLA Medical Center discovered that by temporarily blocking type 1 interferon protein in patients with HIV, the immune system is able to better fight the disease.

The research shows that type 1 interferon, a protein that initiates immune response against viral infections, actually may contribute to the destruction of the immune system in patients with HIV.

"This finding is completely counterintuitive, because many believe that the more interferon at work, the better," Scott Kitchen, associate professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA and senior author of the study, said in a press release.

"We show that the type of interferon being produced during chronic stages of HIV infection has detrimental effects on the body's ability to fight off HIV and other types of infection or cancer and could actually be contributing to accelerated HIV disease."

Research in "humanized mice," which have their immune systems replaced with human immune system cells, showed that temporarily blocking type 1 interferon can restore immune function and speed up viral suppression during treatment with anti-viral drugs for people with HIV.

HIV damages the immune system by destroying CD4 T cells, which are activated during early HIV infection by type 1 interferon. The CD4 T cells signal another type of T cell, CD8, to destroy HIV-infected cells, but HIV evades the CD8 cells by constantly mutating and escaping recognition by CD8 cells and making them ineffective.

This leads to a chronically heightened state of inflammation and activation that causes immune exhaustion and to the destruction of the immune system.

Researchers blocked type 1 interferon in the body to reduce chronic activation of the immune cells to give the exhausted CD8 T cells the chance to rest and restore their ability to fight, which combined with antiretroviral therapy could restore immune function and destroy HIV.

"We found -- counterintuitively -- that blocking this immune response against the virus had beneficial effects in lowering the amounts of virus and increasing the ability of the immune response to clear out the virus," Kitchen, a member of the UCLA AIDS Institute and director of the UCLA Humanized Mouse Core Laboratory, said.

More research is needed before human trials can begin.

"This could have profound implications for the development of therapies that include such approaches as interferon alpha therapy," Anjie Zhen, a postdoctoral scholar and member of the UCLA AIDS Institute and lead author of the study, said in a press release. "This shows that a proper balance is required when administering this type of therapy, where too much can have detrimental effects in suppressing important immune responses."

The study was published in the Journal of Clinical Investigation.